Reticuloendotheliosis viruses (REVs) are a group of avian retroviruses that infect chickens, turkeys, and ducks (1). The prototype virus of this group is reticuloendotheliosis virus strain T(REV-T). REV-T(REV-A) designates a mixture of a replication-defective virus (REV-T) that induces acute neoplastic disease and a nondefective helper virus (REV-A) capable of inducing an immunosuppressive runting disease (2-4). REV-A and other non-defective REVs can be distinguished from REV-T by their ability to replicate in vitro in fibroblasts and their inability to induce acute neoplastic disease in vivo (5, 6). Some non-defective REVs, chick syncytial virus (CSV) and REV-A, induce a bursal-dependent B-cell lymphoma that is indistinguishable from avian leukosis virus (ALV)-induced lymphoid leukosis (6, 7). These tumors develop after a long latent period, are monoclonal and are characterized by proviral insertion within the c-myc locus (8, 9). In contrast, REV-T causes an acute neoplastic disease known as reticuloendotheliosis because the prominent cell in the original neoplastic lesion was morphologically identified as reticuloendothelial (10). These tumors develop rapidly, appear to be polyclonal and are thought to require the expression of the v-rel oncogene carried by REV-T (11, 12).
Despite the original description of the disease, the identity of the tumor induced by v-rel remains unclear. In situ characterization of the in vivo-derived tumor tissue has not been reported. In vitro studies suggest the REV-T-transformed cells are of early lymphoid origin (13, 14), but the absence of specific markers that define this phenotype has prevented conclusive identification. There are two reports of REV-T-derived cell lines which express IgM (14, 15) and it is possible that several phenotypically distinct cells may serve as target cells for v-rel-induced tumors.
REV-A is known to cause thymic and bursal atrophy as well as immunosuppression (2, 17, 18). Since the bursa is the major compartment of B lymphocyte development in the chicken, we reasoned that one consequence of REV-A infection and the subsequent disruption of this organ might be a reduction in B-cell proliferation and differentiation. If REV-T induces lymphoid tumors as suggested by studies of in vitro-derived REV-T cell lines, it is possible that REV-A replication influences the spectrum of lymphoid tumors that develop by reducing the pool of IgM positive B-lymphocytes that are available for REV-T infection. It has been reported that both immunosuppression and bursal atrophy are less severe in CSV-infected chicks (6, 18). We speculated, therefore, that if CSV provided the helper virus functions required for REV-T replication, the pool of cells available for infection by REV-T might contain significantly more IgM positive lymphocytes. Since IgM-positive tumor cell lines have been isolated following REV-T(REV-A) infection, albeit rarely, the present invention involves a prediction that REV-T(CSV) infection would lead to high frequency production of IgM positive B-cell lymphomas.